Methyl iodide → 7-iodo-1-methyl-1H-pyrazolo[4,3-b]pyridine

HRID 1522604Notes

Reaction equation

HRID 1522604 reaction equation
[I:1][C:2]1[C:3]2[C:4](=[CH:8][NH:9][N:10]=2)[N:5]=[CH:6][CH:7]=1.I[CH3:12].[C:13](=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O.C(#N)C.O>[I:1][C:2]1[C:3]2[C:4](=[CH:8][N:9]([CH3:13])[N:10]=2)[N:5]=[CH:6][CH:7]=1.[I:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[N:9][N:10]([CH3:12])[C:3]=12

Participants

8

Reactant 3

HCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 178506553HCID 178506553, compound

Product 2

HCID 674696007-iodo-2-methyl-2H-pyrazolo[4,3-b]pyridineYield 14.19%HCID 674704107-iodo-1-methyl-1H-pyrazolo[4,3-b]pyridineYield 28.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

7-Iodo-2H-pyrazolo[4,3-b]pyridine (100 mg, 0.408 mmol), iodomethane (0.025 ml, 0.408 mmol) and cesium carbonate (266 mg, 0.816 mmol) were combined in DMF (5 mL). The mixture was stirred at room temperature for 1 hour then purified by preparative HPLC eluting with a gradient of 20-70% 10 mmol NH4HCO3 in 20/80 (v/v) water/acetonitrile in 10 mmol NH4HCO3 in water using a Phenomenex Gemini Prep 5 μm C18, 75×30 mm column to give 7-iodo-2-methyl-2H-pyrazolo[4,3-b]pyridine (15 mg, 14.19% yield) and 7-iodo-1-methyl-1H-pyrazolo[4,3-b]pyridine (30 mg, 28.4% yield). MS [M+H] found 260.0. 7-Iodo-2-methyl-2H-pyrazolo[4,3-b]pyridine (15 mg, 0.058 mmol), Tris(dibenzylideneacetone)dipalladium(0) (1.326 mg, 1.448 μmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (8.38 mg, 0.014 mmol), 3′-fluoro-6′-methyl-2,2′-bipyridin-4-amine (11.77 mg, 0.058 mmol) and sodium 2-methylpropan-2-olate (16.69 mg, 0.174 mmol) were combined in dioxane (5 mL). The mixture was heated at 120° C. for 2 hours and then purified by preparative HPLC eluting with a gradient of 5-40% acetonitrile (containing 0.035% TFA) in water (containing 0.05% TFA) using a Sunfire Prep 5 μm C18, 75×30 mm column to afford the title compound as a TFA salt.

Workup

  1. customthen purified by preparative HPLC

Sources & evidence

ORD record
ord-766285b336e0445dbd68e20fa45a5517
Source dataset
uspto-grants-2015_07
Patent number
US09073918B2

Reaction notes

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